Effect of Chewing vs Swallowing Ticagrelor on Platelet Inhibition in Patients With ST-Segment Elevation Myocardial Infarction: A Randomized Clinical Trial

Elad Asher, Shir Tal, Israel Mazin, Arsalan Abu-Much, Avi Sabbag, Moshe Katz, Ehud Regev, Fernando Chernomordik, Victor Guetta, Amit Segev, Dan Elian, Israel Barbash, Paul Fefer, Michael Narodistky, Roy Beigel, Shlomi Matetzky, Elad Asher, Shir Tal, Israel Mazin, Arsalan Abu-Much, Avi Sabbag, Moshe Katz, Ehud Regev, Fernando Chernomordik, Victor Guetta, Amit Segev, Dan Elian, Israel Barbash, Paul Fefer, Michael Narodistky, Roy Beigel, Shlomi Matetzky

Abstract

Importance: Dual anti-platelet therapy represents standard care for treating patients with ST-segment elevation myocardial infarction (STEMI). Ticagrelor is a direct-acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation.

Objective: To evaluate whether chewing a loading dose (LD) of ticagrelor, 180 mg, vs traditional oral administration of an equal dose enhances platelet inhibition at 30 minutes and 1 hour after LD administration in patients with STEMI.

Design, setting, and participants: A randomized clinical trial was conducted in adults aged 30 to 87 years from May to October 2016 in a large tertiary care center. Analyses were intention-to-treat.

Interventions: Fifty patients with STEMI were randomized to either chewing an LD of ticagrelor, 180 mg, or standard oral administration of an equal dose.

Main outcomes and measures: P2Y12 reaction units were evaluated using VerifyNow (Accumentrics) at baseline, 30 minutes, 1 hour, and 4 hours after LD.

Results: Baseline characteristics were similar in both groups. The mean (SD) of P2Y12 reaction units in the chewing group compared with the standard group at baseline, 30 minutes, 1 hour, and 4 hours after ticagrelor LD were 224 (33) vs 219 (44) (95% CI, -16.77 to 27.73; P = .26), 168 (78) vs 230 (69) (95% CI, -103.77 to -19.75; P = .003), 106 (90) vs 181 (89) (95% CI, -125.15 to -26.29; P = .005), and 43 (41) vs 51 (61) (95% CI, -36.34 to 21.14; P = .30), respectively. Platelet reactivity in the chewing group was significantly reduced by 24% at 30 minutes after LD (95% CI, 19.75 to 103.77; P = .001). The relative inhibition of platelet aggregation in the chewing vs the standard group were 51% vs 10% (95% CI, 13.69 to 67.67; P = .005) at 1 hour and 81% vs 76% (95% CI, -12.32 to 16.79; P = .24) at 4 hours, respectively. Major adverse cardiac and cardiovascular event rate at 30 days was low (4%) and occurred in 1 patient in each group (95% CI, 0.06 to 16.93; P > .99).

Conclusions and relevance: Chewing an LD of ticagrelor, 180 mg, in patients with STEMI is feasible and facilitates better early platelet inhibition compared with a standard oral LD. Larger studies are warranted to see if our preliminary findings translate into clinical outcomes.

Trial registration: clinicaltrials.gov Identifier: NCT02725099.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Figures

Figure 1.. CONSORT Flow Diagram
Figure 1.. CONSORT Flow Diagram
GP IIBIIA indicates glycoprotein IIB/IIIA; LD, loading dose; STEMI, ST-segment elevation myocardial infarction.
Figure 2.. Inhibition of Platelet Aggregation in…
Figure 2.. Inhibition of Platelet Aggregation in the Chewing Group vs the Standard Group
IPA indicates inhibition of platelet aggregation; LD, loading dose; PRU, P2Y12 reaction units.

Source: PubMed

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